Nodulation formation efficiency D (NfeD) is a membrane-bound ClpP-class protease; Nodulation formation efficiency D (NfeD; stomatin operon partner protein, STOPP; DUF107) is a member of membrane-anchored ClpP-class proteases. Currently, more than 300 NfeD homologs have been identified - all of which are bacterial or archaeal in origin. Majority of these genomes have been shown to possess operons containing a homologous NfeD/stomatin gene pair, causing NfeD to be previously named STOPP (stomatin operon partner protein). NfeD homologs can be divided into two groups: long and short forms. Long-form homologs have a putative ClpP-class serine protease domain while the short form homologs do not. Downstream from the ClpP-class domain is the so-called NfeD or DUF107 domain. N-terminal region of the NfeD homolog PH1510 (1510-N or PH1510-N) from Pyrococcus horikoshii has been shown to possess serine protease activity and has a Ser-Lys catalytic dyad, preferentially cleaving hydrophobic substrates. Difference in oligomeric form and catalytic residues between 1510-N (forming a dimer) and ClpP (forming a tetradecamer) shows a possible functional difference: 1510-N is likely to have a regulatory function while ClpP is involved in protein quality control.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593  33 VYVIPVEKNVEQGLASFLSRSLQDAKDAHADHIILDINTPGGLVKSAIDMADLITESEIPVTAYVNKRALSAGAYIALQA 112
Cdd:cd07021   1 VYVIPIEGEIDPGLAAFVERALKEAKEEGADAVVLDIDTPGGRVDSALEIVDLILNSPIPTIAYVNDRAASAGALIALAA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593 113 DHIYMAPGGKMGAAAIVDGQGN-AADQKAQSLWLAEMEDAAVKNNRDPKYALAMADPDIDAKEVGAPKGDLLTLNADKAI 191
Cdd:cd07021  81 DEIYMAPGATIGAAEPIPGDGNgAADEKVQSYWRAKMRAAAEKKGRDPDIAEAMVDKDIEVPGVGIKGGELLTLTADEAL 160

                       170
                ....*....|....*...
gi 16079593 192 EVGYSEGTADNLSTLVKK 209
Cdd:cd07021 161 KVGYAEGIAGSLDELLVK 178

signal peptide peptidase SppA, 36K type; The related but duplicated, double-length protein SppA (protease IV) of E. coli was shown experimentally to degrade signal peptides as are released by protein processing and secretion. This protein shows stronger homology to the C-terminal region of SppA than to the N-terminal domain or to the related putative protease SuhB. The member of this family from Bacillus subtilis was shown to have properties consistent with a role in degrading signal peptides after cleavage from precursor proteins, although it was not demonstrated conclusively. [Protein fate, Degradation of proteins, peptides, and glycopeptides]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593    58 KDAHADHIILDINTPGGLVKSAIDMADLITESE--IPVTAYVNKRALSAGAYIALQADHIYMAPGGKMGA 125
Cdd:TIGR00706  28 DDKTIKALVLRINSPGGTVVASEEIYKKLEKLKakKPVVASMGGMAASGGYYISMAADEIFANPGTITGS 97

Nodulation formation efficiency D (NfeD) is a membrane-bound ClpP-class protease; Nodulation formation efficiency D (NfeD; stomatin operon partner protein, STOPP; DUF107) is a member of membrane-anchored ClpP-class proteases. Currently, more than 300 NfeD homologs have been identified - all of which are bacterial or archaeal in origin. Majority of these genomes have been shown to possess operons containing a homologous NfeD/stomatin gene pair, causing NfeD to be previously named STOPP (stomatin operon partner protein). NfeD homologs can be divided into two groups: long and short forms. Long-form homologs have a putative ClpP-class serine protease domain while the short form homologs do not. Downstream from the ClpP-class domain is the so-called NfeD or DUF107 domain. N-terminal region of the NfeD homolog PH1510 (1510-N or PH1510-N) from Pyrococcus horikoshii has been shown to possess serine protease activity and has a Ser-Lys catalytic dyad, preferentially cleaving hydrophobic substrates. Difference in oligomeric form and catalytic residues between 1510-N (forming a dimer) and ClpP (forming a tetradecamer) shows a possible functional difference: 1510-N is likely to have a regulatory function while ClpP is involved in protein quality control.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593  33 VYVIPVEKNVEQGLASFLSRSLQDAKDAHADHIILDINTPGGLVKSAIDMADLITESEIPVTAYVNKRALSAGAYIALQA 112
Cdd:cd07021   1 VYVIPIEGEIDPGLAAFVERALKEAKEEGADAVVLDIDTPGGRVDSALEIVDLILNSPIPTIAYVNDRAASAGALIALAA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593 113 DHIYMAPGGKMGAAAIVDGQGN-AADQKAQSLWLAEMEDAAVKNNRDPKYALAMADPDIDAKEVGAPKGDLLTLNADKAI 191
Cdd:cd07021  81 DEIYMAPGATIGAAEPIPGDGNgAADEKVQSYWRAKMRAAAEKKGRDPDIAEAMVDKDIEVPGVGIKGGELLTLTADEAL 160

                       170
                ....*....|....*...
gi 16079593 192 EVGYSEGTADNLSTLVKK 209
Cdd:cd07021 161 KVGYAEGIAGSLDELLVK 178

Caseinolytic protease (ClpP) is an ATP-dependent protease; Clp protease (caseinolytic protease; ClpP; endopeptidase Clp; Peptidase S14; ATP-dependent protease, ClpAP)-like enzymes are highly conserved serine proteases and belong to the ClpP/Crotonase superfamily. Included in this family are Clp proteases that are involved in a number of cellular processes such as degradation of misfolded proteins, regulation of short-lived proteins and housekeeping removal of dysfunctional proteins. They are also implicated in the control of cell growth, targeting DNA-binding protein from starved cells. The functional Clp protease is comprised of two components: a proteolytic component and one of several regulatory ATPase components, both of which are required for effective levels of protease activity in the presence of ATP. Active site consists of the triad Ser, His and Asp, preferring hydrophobic or non-polar residues at P1 or P1' positions. The protease exists as a tetradecamer made up of two heptameric rings stacked back-to-back such that the catalytic triad of each subunit is located at the interface between three monomers, thus making oligomerization essential for function. Another family included in this class of enzymes is the signal peptide peptidase A (SppA; S49) which is involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. Mutagenesis studies suggest that the catalytic center of SppA comprises a Ser-Lys dyad and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases. In addition to the carboxyl-terminal protease domain that is conserved in all the S49 family members, the E. coli SppA contains an amino-terminal domain. Others, including sohB peptidase, protein C, protein 1510-N and archaeal signal peptide peptidase, do not contain the amino-terminal domain. The third family included in this hierarchy is nodulation formation efficiency D (NfeD) which is a membrane-bound Clp-class protease and only found in bacteria and archaea. Majority of the NfeD genomes have been shown to possess operons containing a homologous NfeD/stomatin gene pair, causing NfeD to be previously named stomatin operon partner protein (STOPP). NfeD homologs can be divided into two groups: long and short forms. Long-form homologs have a putative ClpP-class serine protease domain while the short form homologs do not. Downstream from the ClpP-class domain is the so-called NfeD or DUF107 domain. N-terminal region of the NfeD homolog PH1510 from Pyrococcus horikoshii has been shown to possess serine protease activity having a Ser-Lys catalytic dyad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593  35 VIPVEKNVEQGLASFLSRSLQDAK-DAHADHIILDINTPGGLVKSAIDMADLITESEIPVTAYVNKRALSAGAYIALQAD 113
Cdd:cd00394   1 VIFINGVIEDVSADQLAAQIRFAEaDNSVKAIVLEVNTPGGRVDAGMNIVDALQASRKPVIAYVGGQAASAGYYIATAAN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593 114 HIYMAPGGKMGAAAIVDG-------QGNAADQKAQSLWLAEMEDAAVKNNRDPKYALamadpDIDAKEvgapkgdLLTLN 186
Cdd:cd00394  81 KIVMAPGTRVGSHGPIGGyggngnpTAQEADQRIILYFIARFISLVAENRGQTTEKL-----EEDIEK-------DLVLT 148

                       170
                ....*....|.
gi 16079593 187 ADKAIEVGYSE 197
Cdd:cd00394 149 AQEALEYGLVD 159

Periplasmic serine protease, ClpP class [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593  25 NAKAEKQTVYVIPVEKNVEQGLASF--------LSRSLQDA-KDAHADHIILDINTPGGLVKSAIDMADLIT---ESEIP 92
Cdd:COG0616   4 RPPKVKPSIAVIDLEGTIVDGGGPPsgeigledILAALRKAaEDPDVKAVVLRINSPGGSVAASEEIRDALRrlrAKGKP 83

                        90       100       110
                ....*....|....*....|....*....|..
gi 16079593  93 VTAYVNKRALSAGAYIALQADHIYMAPGGKMG 124
Cdd:COG0616  84 VVASMGDVAASGGYYIASAADKIYANPTTITG 115

Caseinolytic protease (ClpP) is an ATP-dependent, highly conserved serine protease; Clp protease (caseinolytic protease; ClpP; Peptidase S14) is a highly conserved serine protease present throughout in bacteria and eukaryota, but seems to be absent in archaea, mollicutes and some fungi. This subfamily only contains bacterial sequences. Clp proteases are involved in a number of cellular processes such as degradation of misfolded proteins, regulation of short-lived proteins and housekeeping removal of dysfunctional proteins. They are also implicated in the control of cell growth, targeting DNA-binding protein from starved cells. ClpP has also been linked to the tight regulation of virulence genes in the pathogens Listeria monocytogenes and Salmonella typhimurium. This enzyme belong to the family of ATP-dependent proteases; the functional Clp protease is comprised of two components: a proteolytic component and one of several regulatory ATPase components, both of which are required for effective levels of protease activity in the presence of ATP, although the proteolytic subunit alone does possess some catalytic activity. Active site consists of the triad Ser, His and Asp; some members have lost all of these active site residues and are therefore inactive, while others may have one or two large insertions. ClpP seems to prefer hydrophobic or non-polar residues at P1 or P1' positions in its substrate. The protease exists as a tetradecamer made up of two heptameric rings stacked back-to-back such that the catalytic triad of each subunit is located at the interface between three monomers, thus making oligomerization essential for function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593  47 ASFLSRSLQDAKDAhaDHIILDINTPGGLVKSAIDMADLITESEIPVTAYVNKRALSAGAYIALQADHIYMAPGGKM--- 123
Cdd:cd07016  17 AKEFKDALDALGDD--SDITVRINSPGGDVFAGLAIYNALKRHKGKVTVKIDGLAASAASVIAMAGDEVEMPPNAMLmih 94

                        90       100       110
                ....*....|....*....|....*....|.
gi 16079593 124 GAAAIVDgqGNAADQKAQSLWLAEMEDAAVK 154
Cdd:cd07016  95 NPSTGAA--GNADDLRKAADLLDKIDESIAN 123

Serine dehydrogenase proteinase; This family of archaebacterial proteins, formerly known as DUF114, has been found to be a serine dehydrogenase proteinase distantly related to ClpP proteinases that belong to the serine proteinase superfamily. The family has a catalytic triad of Ser, Asp, His residues, which shows an altered residue ordering compared with the ClpP proteinases but similar to that of the carboxypeptidase clan.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593    65 IILDINTPGGLVKSAIDMADLITESEIPVTAYVNKRALSAGAYIALQADHIYMAPGGKMG----------AAAIVDG--Q 132
Cdd:pfam01972  94 IDLIIHTPGGLALAATQIAKALKEHKAKTTVIVPHYAMSGGTLIALAADEIIMDENAVLGpvdpqigqypAASILKAveK 173

                          90       100       110
                  ....*....|....*....|....*....|.
gi 16079593   133 GNAADQKAQSLWLAEMEDAAVKNNRDPKYAL 163
Cdd:pfam01972 174 KGPKKIDDQTLILADISKKAIKQMEEFVYNL 204

Signal peptide peptidase A; Signal peptide peptidase A (SppA; Peptidase S49; Protease IV): SppA is an intramembrane enzyme found in all three domains of life and is involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. Unlike the eukaryotic functional homologs that are proposed to be aspartic proteases, site-directed mutagenesis and sequence analysis have shown these bacterial, archaeal and thylakoid SppAs to be ClpP-like serine proteases. The predicted active site serine for members in this family occurs in a transmembrane domain, cleaving peptide bonds in the plane of the lipid bilayer. Mutagenesis studies also suggest that the catalytic center comprises a Ser-Lys dyad (both residues absolutely conserved within bacteria, chloroplast and mitochondrial signal peptidase family members) and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases. In addition to the carboxyl-terminal protease domain that is conserved in all the S49 family members, the E. coli SppA contains an amino-terminal domain (sometimes referred to as 67K type). Others, including sohB peptidase, protein C, protein 1510-N and archaeal signal peptide peptidase, do not contain the amino-terminal domain (sometimes referred to as 36K type). Interestingly, the single membrane spanning E. coli SppA carries out catalysis using a Ser-Lys dyad with the serine located in the conserved carboxy-terminal protease domain and the lysine in the non-conserved amino-terminal domain. This family also contains homologs that either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity of peptidases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16079593  50 LSRSLQDAK-DAHADHIILDINTPGGLVKSAIDMADLITESEI---PVTAYVNKRALSAGAYIALQADHIYMAPggkmga 125
Cdd:cd07014  27 TAAQIRDARlDPKVKAIVLRVNSPGGSVTASEVIRAELAAARAagkPVVASGGGNAASGGYWISTPANYIVANP------ 100

                        90       100
                ....*....|....*....|...
gi 16079593 126 AAIVDGQGNAADQKAQSLWLAEM 148
Cdd:cd07014 101 STLVGSIGIFGVQLADQLSIENG 123

Signal peptide peptidase A (SppA), a serine protease, has catalytic Ser-Lys dyad; Signal peptide peptidase A (SppA; Peptidase S49; Protease IV): SppAs in this subfamily are found in all three domains of life and are involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. Site-directed mutagenesis and sequence analysis have shown these bacterial, archaeal and thylakoid SppAs to be serine proteases. The predicted active site serine for members in this family occurs in a transmembrane domain. Mutagenesis studies also suggest that the catalytic center comprises a Ser-Lys dyad (both residues absolutely conserved within bacteria, chloroplast and mitochondrial signal peptidase family members) and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases. In addition to the carboxyl-terminal protease domain that is conserved in all the S49 family members, the E. coli SppA contains an amino-terminal domain, similar to Arabidopsis thaliana SppA1 peptidase. Others, including sohB peptidase, protein C and archaeal signal peptide peptidase, do not contain the amino-terminal domain. Interestingly, the single membrane spanning E. coli SppA carries out catalysis using a Ser-Lys dyad with the serine located in the conserved carboxy-terminal protease domain and the lysine in the non-conserved amino-terminal domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 16079593  57 AKDAHADHIILDINTPGGLVKSAIDMADLITESEI---PVTAYVNKRALSAGAYIALQADHIYMAPGGKMGAAAIV 129
Cdd:cd07019  34 RLDPKVKAIVLRVNSPGGSVTASEVIRAELAAARAagkPVVVSAGGAAASGGYWISTPANYIVANPSTLTGSIGIF 109

C-terminal processing peptidase; serine protease family S41; The C-terminal processing peptidase (CPP, EC 3.4.21.102) also known as tail-specific protease (tsp), the photosystem II D1 C-terminal processing protease (D1P), and other related S41 protease family members are present in this CD. CPP is synthesized as a precursor form with a carboxyl-terminal extension. It specifically recognizes a C-terminal tripeptide, Xaa-Yaa-Zaa, in which Xaa is preferably Ala or Leu, Yaa is preferably Ala or Tyr and Zaa is preferably Ala, but then cleaves at a variable distance from the C-terminus. The C-terminal carboxylate group is essential, and proteins where this group is amidated are not substrates. This family of proteases contains the PDZ domain that promotes protein-protein interactions and is important for substrate recognition. The active site consists of a serine/lysine catalytic dyad. The bacterial CCP-1 is believed to be important for the degradation of incorrectly synthesized proteins as well as protection from thermal and osmotic stresses. In E. coli, it is involved in the cleavage of a C-terminal peptide of 11 residues from the precursor form of penicillin-binding protein 3 (PBP3). In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II, allowing the light-driven assembly of the tetranuclear manganese cluster, which is responsible for photosynthetic water oxidation.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 16079593  50 LSRSLQDAKDAHADHIILDI-NTPGGLVKSAIDMADL 85
Cdd:cd07560  66 LKKALKELKKQGMKGLILDLrNNPGGLLDEAVEIADL 102